BACKGROUND Cholangiocarcinoma(CCA)poses a significant clinical challenge due to its low radical resection rate and a propensity for high postoperative recurrence,resulting in a poor dismal.Although the combination of ...BACKGROUND Cholangiocarcinoma(CCA)poses a significant clinical challenge due to its low radical resection rate and a propensity for high postoperative recurrence,resulting in a poor dismal.Although the combination of targeted therapy and immunotherapy has demonstrated notable efficacy in several solid tumors recently,however,its application in CCA remains underexplored and poorly documented.CASE SUMMARY This case report describes a patient diagnosed with stage IV CCA,accompanied by liver and abdominal wall metastases,who underwent palliative surgery.Subsequently,the patient received two cycles of treatment combining lenvatinib with sintilimab,which resulted in a reduction in abdominal wall metastasis,while intrahepatic metastasis displayed progression.This unexpected observation illustrates different responses of intrahepatic and extrahepatic metastases to the same therapy.CONCLUSION Lenvatinib combined with sintilimab shows promise as a potential treatment strategy for advanced CCA.Genetic testing for related driver and/or passenger mutations,as well as an analysis of tumor immune microenvironment analysis,is crucial for optimizing drug combinations and eventually addressing the issue of non-response in specific metastatic sites.展开更多
Insulin-like growth factor 1 （IGF-I） is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half- life, rapid clearance, and limited target specificity. To achieve t...Insulin-like growth factor 1 （IGF-I） is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half- life, rapid clearance, and limited target specificity. To achieve targeted and long-lasting treatment, we investigated the addition of a binding structure by fusing a collagen-binding domain to IGF- 1. After confirming its affinity for collagen, the biological activity of this construct was examined by measuring cell proliferation after transfection into PC12 and Schwann cells using a 3-（4,5-dimethyl-2-thiazolyl）-2,5-di- phenyl-2-H-tetrazolium bromide assay. Immunofluorescence staining was conducted to detect neurofilament and microtubule-associated protein 2 expression, while real time-polymerase chain reaction was utilized to determine IGF-1 receptor and nerve growth/actor mRNA expression. Our results demonstrate a significant increase in collagen-binding activity of the recombinant protein compared with IGF-1. Moreover, the recombinant protein promoted proliferation of PC12 and Schwann cells, and increased the expression of neurofilament and microtubule-associated protein 2. Importantly, the recombinant protein also stimulated sustained expression of IGF-1 receptor and nerve growth factor mRNA for days. These results show that the recombinant protein achieved the goal of targeting and long-lasting treatment, and thus could become a clinically used factor for promoting nerve regeneration with a prolonged therapeutic effect.展开更多
Particle swarm optimization (PSO) is an efficient, robust and simple optimization algorithm. Most studies are mainly concentrated on better understanding of the standard PSO control parameters, such as acceleration co...Particle swarm optimization (PSO) is an efficient, robust and simple optimization algorithm. Most studies are mainly concentrated on better understanding of the standard PSO control parameters, such as acceleration coefficients, etc. In this paper, a more simple strategy of PSO algorithm called θ-PSO is proposed. In θ-PSO, an increment of phase angle vector replaces the increment of velocity vector and the positions are decided by the mapping of phase angles. Benchmark testing of nonlinear func- tions is described and the results show that the performance of θ-PSO is much more effective than that of the standard PSO.展开更多
AIM： To characterize the tumor suppressor gene P53 mutations and study the correlation of P53 gene mutation and the expression of P53 protein in cholangiocarcinoma. METHODS： A total of 36 unselected, frozen samples ...AIM： To characterize the tumor suppressor gene P53 mutations and study the correlation of P53 gene mutation and the expression of P53 protein in cholangiocarcinoma. METHODS： A total of 36 unselected, frozen samples of cholangiocarcinoma were collected, p53 gene status（exon 5-8） and P53 protein were examined by automated sequencing and immunohistochemical staining, combined with the clinical parameters of patients. RESULTS： P53 gene mutations were found in 22 of 36 （61.1%） patients. Nineteen of 36 （52.8%） patients were positive for P53 protein expression. There were significant differences in extent of differentiation and invasion between the positive and negative expression of P53 protein. However, there were no significant differences in pathologic parameters between the mutations and non-mutations. CONCLUSION： The alterations of the P53 gene evaluated by DNA sequence analysis is relatively accurate. Expression of P53 protein could not act as an independent index to estimate the prognosis of cholangiocarcinoma.展开更多
A method of continuous-discontinuous cellular automaton for modeling the growth and coalescence of multiple cracks in brittle material is presented. The method uses the level set to track arbitrary discontinuities, an...A method of continuous-discontinuous cellular automaton for modeling the growth and coalescence of multiple cracks in brittle material is presented. The method uses the level set to track arbitrary discontinuities, and calculation grids are independent of the discontinuities and no remeshing are required with the crack growing. Based on Grif- fith fracture theory and Mohr-Coulumb criterion, a mixed fracture criterion for multiple cracks growth in brittle mate- rial is proposed. The method treats the junction and coales- cence of multiple cracks, and junction criterion and coales- cence criterion for brittle material are given, too. Besides, in order to overcome the tracking error in the level set ap- proximation for crack junction and coalescence, a dichotomy searching algorithm is proposed. Introduced the above the- ories into continuous-discontinuous cellular automaton, the present method can be applied to solving multiple crack growth in brittle material, and only cell stiffness is needed and no assembled global stiffness is needed. Some numerical examples are given to shown that the present method is efficient and accurate for crack junction, coalescence and percolation problems.展开更多
Excavation Damaged Zone(EDZ)scope is important for optimizing excavation and support schemes in deep underground caverns.However,accurately predicting the full EDZ scope within the surrounding rock masses of deep unde...Excavation Damaged Zone(EDZ)scope is important for optimizing excavation and support schemes in deep underground caverns.However,accurately predicting the full EDZ scope within the surrounding rock masses of deep underground caverns during excavation remains a pressing problem.This study presents a comprehensive EDZ scope prediction approach(CESPA)for the brittle surrounding rock masses of deep underground caverns by coupling numerical simulation with quantitative analysis of borehole wall images and ultrasonic test results.First,the changes in both P-velocity(V_(p))and joint distribution of the surrounding rock masses before and after excavation damage are captured using ultrasonic tests and borehole digital cameras.Second,the quality Q-parameters of the surrounding rock mass before and after excavation damage are preliminarily rated with the rock mass descriptions provided by borehole wall images,and the rock mass V_(p)-parameter values are determined according to the V_(p)-borehole depth curves.Third,the Q-parameter ratings are further finely adjusted by updating the related Q-values to be similar with the Q-values estimated by V_(p)-parameter values.Fourth,the initial and residual mechanical parameters for the rock mass deterioration model(RDM)are estimated by the adjusted Q-parameter ratings based on the modified Q-based relations,and the elastic modulus deterioration index(EDI)threshold to describe the EDZ boundary is determined with the V_(p)-parameter values.Finally,EDZ scope is predicted using the elastoplastic numerical simulation with RDM and EDI based on the mechanical parameter estimates and EDI threshold.Analyses of applications in Sub-lab D1 in Jinping II project show that CESPA can provide a reliable and operable solution for predicting full EDZ scopes within the brittle surrounding rock masses of deep underground caverns.展开更多
AIM To retrospectively review patients with chronic pancreatitis(CP) treated with Frey's procedures between January 2009 and January 2014.METHODS A retrospective review was performed of patients with CP treated wi...AIM To retrospectively review patients with chronic pancreatitis(CP) treated with Frey's procedures between January 2009 and January 2014.METHODS A retrospective review was performed of patients with CP treated with Frey's procedures between January 2009 and January 2014 in the Department of Pancreatic Surgery. A cross-sectional study of postoperative pain relief, quality of life(Qo L), and alcohol and nicotine abuse was performed by clinical interview, letters and telephone interview in January 2016. Qo L of patients was evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30) version 3.0. The patients were requested to fill in the questionnaires by themselves via correspondence or clinical interview.RESULTS A total of 80 patients were enrolled for analysis, including 44 who underwent the original Frey's procedure and 36 who underwent a modified Frey's procedure. The mean age was 46 years in the original group and 48 years in the modified group. Thirtyfive male patients(80%) were in the original group and 33(92%) in the modified group. There were no differences in the operating time, blood loss, and postoperative morbidity and mortality between the two groups. The mean follow-up was 50.3 mo in the original group and 48.7 mo in the modified group. There were no differences in endocrine and exocrine function preservation between the two groups. The original Frey's procedure resulted in significantly betterpain relief, as shown by 5-year follow-up(P = 0.032), better emotional status(P = 0.047) and fewer fatigue symptoms(P = 0.028). When stratifying these patients by the M-ANNHEIM severity index, no impact was found on pain relief after the two types of surgery.CONCLUSION The original Frey's procedure is as safe as the modified procedure, but the former yields better pain relief. The severity of CP does not affect postoperative pain relief.展开更多
Objective: To study the effects of balance exercise training on chronic nerve injury, GLP-1 and inflammatory mediator secretion in patients with senile dementia. Methods: Patients with senile dementia who were treated...Objective: To study the effects of balance exercise training on chronic nerve injury, GLP-1 and inflammatory mediator secretion in patients with senile dementia. Methods: Patients with senile dementia who were treated in the Fourth People's Hospital of Ya'an between February 2015 and January 2018 were chosen as the research subjects and randomly divided into two groups, the experimental group received balance exercise training and the control group received routine intervention. The levels of chronic nerve injury indexes, GLP-1 and inflammatory cytokines in serum as well as the expression of inflammatory signaling molecules in peripheral blood were determined before and after intervention. Results:Compared with those of same group before intervention, serum Hcy, Aβ1-42, Tau, IL-1β, IL-18, TNF-α and IFN-γ levels as well as peripheral blood NLRP3, Caspase-1 and DOCK2 expression intensity of both groups were decreasing whereas serum SOD, PON1 and GLP-1 levels as well as peripheral blood PKA and CREB expression intensity were increasing after intervention, and serum Hcy, Aβ1-42, Tau, IL-1β, IL-18, TNF-α and IFN-γ levels as well as peripheral blood NLRP3, Caspase-1 and DOCK2 expression intensity of experimental group after intervention were lower than those of control group whereas serum SOD, PON1 and GLP-1 levels as well as peripheral blood PKA and CREB expression intensity were higher than those of control group. Conclusion: Balance exercise training can reduce the chronic nerve injury and regulate the secretion of GLP-1 and inflammatory mediators in patients with senile dementia.展开更多
文摘BACKGROUND Cholangiocarcinoma(CCA)poses a significant clinical challenge due to its low radical resection rate and a propensity for high postoperative recurrence,resulting in a poor dismal.Although the combination of targeted therapy and immunotherapy has demonstrated notable efficacy in several solid tumors recently,however,its application in CCA remains underexplored and poorly documented.CASE SUMMARY This case report describes a patient diagnosed with stage IV CCA,accompanied by liver and abdominal wall metastases,who underwent palliative surgery.Subsequently,the patient received two cycles of treatment combining lenvatinib with sintilimab,which resulted in a reduction in abdominal wall metastasis,while intrahepatic metastasis displayed progression.This unexpected observation illustrates different responses of intrahepatic and extrahepatic metastases to the same therapy.CONCLUSION Lenvatinib combined with sintilimab shows promise as a potential treatment strategy for advanced CCA.Genetic testing for related driver and/or passenger mutations,as well as an analysis of tumor immune microenvironment analysis,is crucial for optimizing drug combinations and eventually addressing the issue of non-response in specific metastatic sites.
基金supported by the National Natural Science Foundation of China,No.81350013a grant from the Jilin Provincial Science and Technology Plan of China,No.20160101027JC&SC201502001the Graduate Innovation Fund of Jilin University in China,No.2017031&2017176
文摘Insulin-like growth factor 1 （IGF-I） is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half- life, rapid clearance, and limited target specificity. To achieve targeted and long-lasting treatment, we investigated the addition of a binding structure by fusing a collagen-binding domain to IGF- 1. After confirming its affinity for collagen, the biological activity of this construct was examined by measuring cell proliferation after transfection into PC12 and Schwann cells using a 3-（4,5-dimethyl-2-thiazolyl）-2,5-di- phenyl-2-H-tetrazolium bromide assay. Immunofluorescence staining was conducted to detect neurofilament and microtubule-associated protein 2 expression, while real time-polymerase chain reaction was utilized to determine IGF-1 receptor and nerve growth/actor mRNA expression. Our results demonstrate a significant increase in collagen-binding activity of the recombinant protein compared with IGF-1. Moreover, the recombinant protein promoted proliferation of PC12 and Schwann cells, and increased the expression of neurofilament and microtubule-associated protein 2. Importantly, the recombinant protein also stimulated sustained expression of IGF-1 receptor and nerve growth factor mRNA for days. These results show that the recombinant protein achieved the goal of targeting and long-lasting treatment, and thus could become a clinically used factor for promoting nerve regeneration with a prolonged therapeutic effect.
基金the National Natural Science Foundation of China (Nos. 60625302 and 60704028)the Program for ChangjiangScholars and Innovative Research Team in University (No. IRT0721)+2 种基金the 111 Project (No. B08021)the Major State Basic Research De-velopment Program of Shanghai (No. 07JC14016)ShanghaiLeading Academic Discipline Project (No. B504) of China
文摘Particle swarm optimization (PSO) is an efficient, robust and simple optimization algorithm. Most studies are mainly concentrated on better understanding of the standard PSO control parameters, such as acceleration coefficients, etc. In this paper, a more simple strategy of PSO algorithm called θ-PSO is proposed. In θ-PSO, an increment of phase angle vector replaces the increment of velocity vector and the positions are decided by the mapping of phase angles. Benchmark testing of nonlinear func- tions is described and the results show that the performance of θ-PSO is much more effective than that of the standard PSO.
基金a grant from Outstanding Youth Foundation of Shandong Province, China, No. 2005BS02008
文摘AIM： To characterize the tumor suppressor gene P53 mutations and study the correlation of P53 gene mutation and the expression of P53 protein in cholangiocarcinoma. METHODS： A total of 36 unselected, frozen samples of cholangiocarcinoma were collected, p53 gene status（exon 5-8） and P53 protein were examined by automated sequencing and immunohistochemical staining, combined with the clinical parameters of patients. RESULTS： P53 gene mutations were found in 22 of 36 （61.1%） patients. Nineteen of 36 （52.8%） patients were positive for P53 protein expression. There were significant differences in extent of differentiation and invasion between the positive and negative expression of P53 protein. However, there were no significant differences in pathologic parameters between the mutations and non-mutations. CONCLUSION： The alterations of the P53 gene evaluated by DNA sequence analysis is relatively accurate. Expression of P53 protein could not act as an independent index to estimate the prognosis of cholangiocarcinoma.
基金supported by the National Key Basic Research Program of China(2013CB036405)the National Natural Science Foundation of China(11002154,41272349,and 41372315)the CAS/SAFEA International Partnership Program for Creative Research Teams(KZCX2-YW-T12)
文摘A method of continuous-discontinuous cellular automaton for modeling the growth and coalescence of multiple cracks in brittle material is presented. The method uses the level set to track arbitrary discontinuities, and calculation grids are independent of the discontinuities and no remeshing are required with the crack growing. Based on Grif- fith fracture theory and Mohr-Coulumb criterion, a mixed fracture criterion for multiple cracks growth in brittle mate- rial is proposed. The method treats the junction and coales- cence of multiple cracks, and junction criterion and coales- cence criterion for brittle material are given, too. Besides, in order to overcome the tracking error in the level set ap- proximation for crack junction and coalescence, a dichotomy searching algorithm is proposed. Introduced the above the- ories into continuous-discontinuous cellular automaton, the present method can be applied to solving multiple crack growth in brittle material, and only cell stiffness is needed and no assembled global stiffness is needed. Some numerical examples are given to shown that the present method is efficient and accurate for crack junction, coalescence and percolation problems.
基金funded by the National Natural Science Foundation of China under Grant Nos.51979268,U1765206,41877256。
文摘Excavation Damaged Zone(EDZ)scope is important for optimizing excavation and support schemes in deep underground caverns.However,accurately predicting the full EDZ scope within the surrounding rock masses of deep underground caverns during excavation remains a pressing problem.This study presents a comprehensive EDZ scope prediction approach(CESPA)for the brittle surrounding rock masses of deep underground caverns by coupling numerical simulation with quantitative analysis of borehole wall images and ultrasonic test results.First,the changes in both P-velocity(V_(p))and joint distribution of the surrounding rock masses before and after excavation damage are captured using ultrasonic tests and borehole digital cameras.Second,the quality Q-parameters of the surrounding rock mass before and after excavation damage are preliminarily rated with the rock mass descriptions provided by borehole wall images,and the rock mass V_(p)-parameter values are determined according to the V_(p)-borehole depth curves.Third,the Q-parameter ratings are further finely adjusted by updating the related Q-values to be similar with the Q-values estimated by V_(p)-parameter values.Fourth,the initial and residual mechanical parameters for the rock mass deterioration model(RDM)are estimated by the adjusted Q-parameter ratings based on the modified Q-based relations,and the elastic modulus deterioration index(EDI)threshold to describe the EDZ boundary is determined with the V_(p)-parameter values.Finally,EDZ scope is predicted using the elastoplastic numerical simulation with RDM and EDI based on the mechanical parameter estimates and EDI threshold.Analyses of applications in Sub-lab D1 in Jinping II project show that CESPA can provide a reliable and operable solution for predicting full EDZ scopes within the brittle surrounding rock masses of deep underground caverns.
文摘AIM To retrospectively review patients with chronic pancreatitis(CP) treated with Frey's procedures between January 2009 and January 2014.METHODS A retrospective review was performed of patients with CP treated with Frey's procedures between January 2009 and January 2014 in the Department of Pancreatic Surgery. A cross-sectional study of postoperative pain relief, quality of life(Qo L), and alcohol and nicotine abuse was performed by clinical interview, letters and telephone interview in January 2016. Qo L of patients was evaluated with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30) version 3.0. The patients were requested to fill in the questionnaires by themselves via correspondence or clinical interview.RESULTS A total of 80 patients were enrolled for analysis, including 44 who underwent the original Frey's procedure and 36 who underwent a modified Frey's procedure. The mean age was 46 years in the original group and 48 years in the modified group. Thirtyfive male patients(80%) were in the original group and 33(92%) in the modified group. There were no differences in the operating time, blood loss, and postoperative morbidity and mortality between the two groups. The mean follow-up was 50.3 mo in the original group and 48.7 mo in the modified group. There were no differences in endocrine and exocrine function preservation between the two groups. The original Frey's procedure resulted in significantly betterpain relief, as shown by 5-year follow-up(P = 0.032), better emotional status(P = 0.047) and fewer fatigue symptoms(P = 0.028). When stratifying these patients by the M-ANNHEIM severity index, no impact was found on pain relief after the two types of surgery.CONCLUSION The original Frey's procedure is as safe as the modified procedure, but the former yields better pain relief. The severity of CP does not affect postoperative pain relief.
文摘Objective: To study the effects of balance exercise training on chronic nerve injury, GLP-1 and inflammatory mediator secretion in patients with senile dementia. Methods: Patients with senile dementia who were treated in the Fourth People's Hospital of Ya'an between February 2015 and January 2018 were chosen as the research subjects and randomly divided into two groups, the experimental group received balance exercise training and the control group received routine intervention. The levels of chronic nerve injury indexes, GLP-1 and inflammatory cytokines in serum as well as the expression of inflammatory signaling molecules in peripheral blood were determined before and after intervention. Results:Compared with those of same group before intervention, serum Hcy, Aβ1-42, Tau, IL-1β, IL-18, TNF-α and IFN-γ levels as well as peripheral blood NLRP3, Caspase-1 and DOCK2 expression intensity of both groups were decreasing whereas serum SOD, PON1 and GLP-1 levels as well as peripheral blood PKA and CREB expression intensity were increasing after intervention, and serum Hcy, Aβ1-42, Tau, IL-1β, IL-18, TNF-α and IFN-γ levels as well as peripheral blood NLRP3, Caspase-1 and DOCK2 expression intensity of experimental group after intervention were lower than those of control group whereas serum SOD, PON1 and GLP-1 levels as well as peripheral blood PKA and CREB expression intensity were higher than those of control group. Conclusion: Balance exercise training can reduce the chronic nerve injury and regulate the secretion of GLP-1 and inflammatory mediators in patients with senile dementia.
